[Boerhaave syndrome and pregnancy. A case report and review of the literature]. / Syndrome de Boerhaave et grossesse. A propos d'un cas et revue de la littérature.

The syndrome of Boerhaave is a rare affection, corresponding to a spontaneous rupture of the oesophagus, the prognosis of which depends on the precocity of cares. Clinically, it is characterized by a set of three: efforts of vomitings, thoracic pain and subcutaneous emphysema. We report the first case of spontaneous rupture of the oesophagus in a 3-month pregnant woman, further to incoercible vomiting. The excellent clinical tolerance of the patient has allowed a medical care with strict monitoring, parenteral food and adapted antibiotic therapy. The surgery as a matter of urgency, usually indicated in this pathology, was not realized in this context of pregnancy. The obstetric and neonatal future was favorable. We discuss the diagnostic difficulties, the modalities of cares as well as the prognosis of such a pathology.

[Primary lung cancer in elderly subjects in France]. / Le cancer bronchique primitif du sujet âgé en France. Résultats de l'étude KBP-2000 du Collège des Pneumologues des Hôpitaux Généraux (CPHG).

INTRODUCTION: There are few data on primary bronchial carcinoma in France. We report here the results of the study KBP 2000-CPHG in which there were 1868 patients aged 70 or more and 338 aged 80 or more. METHODS: We compared the patients under 70 (Group I) with those aged 70 or more (Group II) as well as with the details of the over 80's. RESULTS: Group II included significantly more women (17.4% vs 15.2%; p = 0.04), non-smokers (11.2% vs 5.3%; p<0.0001), patients of poor performance status (24.2% vs 14.5%; p<0.0001) and squamous carcinomas (44.5% vs 37.8%; p<0.001) than Group I, but fewer adenocarcinomas (27.2% vs 31.5%; p = 0.009) and as many small cell carcinomas (15.9% vs 16.9%; p = 0.32). In Group II there were less stage III and IV tumours (75.1% vs 78.1%; p = 0.0005) more symptomatic treatment (23.2% vs 6.1%) and radiotherapy alone (12.8% vs 3.8%; p < 0.0001). The results were similar beyond 80 years. On multivariate analysis age, performance status and stage appeared to be independent variables in the choice of curative or symptomatic treatment. CONCLUSIONS: Age alone is not therefore a limiting factor in the choice of treatment.

[Primary bronchial carcinoma in elderly subjects in France]. / Le cancer bronchique primitif du sujet âgé en France. Résultats de l'étude KBP-2000 du Collège des Pneumologues des Hôpitaux Généraux (CPHG).

INTRODUCTION: There are few data on primary bronchial carcinoma in France. We report here the results of the study KBP 2000-CPHG in which there were 1868 patients aged 70 or more and 338 aged 80 or more. METHODS: We compared the patients under 70 (Group I) with those aged 70 or more (Group II) as well as with the details of the over 80's. RESULTS: Group II included significantly more women (17.4% vs 15.2%; p=0.04), non-smokers (11.2% vs 5.3%; p<0.0001), patients of poor performance status (24.2% vs 14.5%; p<0.0001) and squamous carcinomas (44.5% vs 37.8%; p<0.001) than Group I, but fewer adenocarcinomas (27.2% vs 31.5%; p=0.009) and as many small cell carcinomas (15.9% vs 16.9%; p=0.32). In Group II there were less stage III and IV tumours (75.1% vs 78.1%; p=0.0005) more symptomatic treatment (23.2% vs 6.1%) and radiotherapy alone (12.8% vs 3.8%; p<0.0001). The results were similar beyond 80 years. On multivariate analysis age, performance status and stage appeared to be independent variables in the choice of curative or symptomatic treatment. CONCLUSIONS: Age alone is not therefore a limiting factor in the choice of treatment.

Carboplatin-etoposide combination in small cell lung cancer patients older than 70 years: a phase II trial.

BACKGROUND: No standard treatment is defined for elderly patients with small cell lung cancer (SCLC). Carboplatin and etoposide are highly active agents against SCLC. In this study, we evaluated the activity and toxicity of a combination of these two agents. PATIENTS AND METHODS: Thirty-four untreated patients with limited or extensive SCLC and median age of 73.9 years entered the study. Chemotherapy consisted of carboplatin i.v. on day 1 (AUC 5 using Calvert's formula) and etoposide 100 mg/m(2) given orally on days 1-5, every 4 weeks, and thoracic irradiation was given to limited disease patients after chemotherapy. RESULTS: The overall response rates was 59% (95% CI: 43-76). The median survival for all patients was 37 weeks (range 3-76 weeks). The toxicity was mainly haematological with grade 3-4 neutropenia in 59% of courses, febrile neutropenia in 15% of courses, and toxic death in 9% of patients. CONCLUSION: The results of this regimen are disappointing with worse response and survival, and more haematological toxicity than expected and previously reported, despite the use of Calvert's formula. Possible explanations are the use of etoposide per os rather than i.v., the frequent comorbidities of older patients and the inclusion of patients with poor prognosis factors.

Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1.

PURPOSE: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis. PATIENTS AND METHODS: One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m2 on day 1 and vinorelbine 30 mg/m2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids. (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B). RESULTS: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with 1 complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities. CONCLUSIONS: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.

The prognostic value of etoposide area under the curve (AUC) at first chemotherapy cycle in small cell lung cancer patients: a multicenter study of the groupe Lyon-Saint-Etienne d'Oncologie Thoracique (GLOT).

PURPOSE: To assess the potential relationships between systemic exposure to doxorubicin, etoposide and ifosfamide at first chemotherapy cycle and therapeutic effect, tumor response, toxicity, and survival, in small cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Twenty-four patients referred to five different centers with either thorax-limited or metastatic SCLC entered the study. All but one received two induction courses of the 3 day-AVI (doxorubicin 50 mg/m(2) day 1, etoposide 120 mg/m(2) day 1, 2, 3, ifosfamide 2000 mg/m(2) day 1, 2) regimen. Individual plasma samples were collected at the first course and complete concentration data on 24 courses were available. Drugs exposures were estimated using a population pharmacokinetic method and expressed as clearance (Cl), area under the curve (AUC), and AUC-intensity (AUC/cycle duration). Responding patients received thoracic irradiation+concomitant cisplatinum-etoposide (limited disease) or four more courses of AVI (extensive disease). The impact of exposure parameters on haematological toxicity, tumor response and overall survival was assessed using linear regression, the Mann-Whitney U-test and the log-rank test/Kaplan-Meier estimation, respectively. RESULTS: Twenty-three patients could be evaluated for response and survival. We found no relationship between drug exposure and haematological toxicity but all patients had received Granulocyte-Colony Stimulating Factor support. Tumor response was marginally influenced by ifosfamide AUC. In patients with etoposide AUC>254.8 mg h/l, 1-year survival was 50.0 vs. 9.1% in the other group (median 11.4 vs. 7.1 months, P=0.02), with respect to established prognostic factors. In patients with extensive disease only (n=15), 1-year survival was 42.9 vs. 0% (median 11.3 vs. 5.3 months, P=0.01). CONCLUSION: This study strongly suggests that SCLC patients should benefit from sufficient etoposide exposure at first cycle to improve survival. Adaptative control based on plasma concentration measurements should be tested in further studies assessing various polychemotherapy regimens.

Population pharmacokinetics of doxorubicin, etoposide and ifosfamide in small cell lung cancer patients: results of a multicentre study.

AIMS: To determine the population pharmacokinetic (PK) parameters of doxorubicin (Dox), etoposide (Eto) and ifosfamide (Ifo) in small cell lung cancer (SCLC) patients, to assess the potential relationship between those parameters and to estimate the impact of individual morphological and biological covariates on patients' PK parameters. METHODS: Twenty-four patients with either SCLC limited to the thorax or extensive SCLC entered the study. All but one received at least two 3 day courses of the standard AVI (Dox 50 mg m-2 day 1, Eto 120 mg m-2 day 1,2,3, Ifo 2000 mg m-2 day 1,2) regimen. Individual blood samples were collected during each course and data on 47 courses were available. Data were analysed with the NONMEM program. Dox, Eto and Ifo plasma concentrations were studied with multicompartment (3, 2 and 2, respectively) models. Inter-individual and interoccasion (course-to-course) variabilities were estimated. The influence of individual covariates (age, sex, stage of the disease, weight, height, body-surface area, serum creatinine, total protein, LDH, ASAT, ALAT, alkaline phosphatase, gamma-GT, bilirubin) on PK parameters was also assessed. Correlations between individual PK parameters of Dox, Eto and Ifo were explored by using Pearson's correlation coefficient. RESULTS: Multiple data were available for each patient. Dox clearance (CL) and volume of distribution (Vd) were 32.0 l h-1 and 9.3 l (Inter-individual variability: 17.2% and 19.2%). Eto CL (l h-1) and Vd were, respectively, 3.34-0.0083* serum creatinine (micromol l-1) and 6.38 l (interindividual variability: 15.6% and 18.7%). Ifo CL and Vd at day 1 were 5.6 l h-1 and 26.0 l (interindividual variability: 10.1% and 17.2%, respectively). Estimation of course-to-course variability improved the precision of PK models in some cases. No correlation was observed between the respective PK parameters of each drug. Of individual covariates tested, only serum creatinine correlated with Eto CL (r = -0.37, P < 0.001). Self-induction of the metabolism of Ifo was apparent (mean CL increase from day 1 to day 2 : 42%) and individually correlated with the CL value at day 1 (r = -0.61, P < 0.001). CONCLUSIONS: Assessment of potential relationships between individual systemic exposure of chemotherapy and therapeutic endpoints (tumour response, toxicity and survival) will be required to adjust drugs dosages based on individual PK parameters rather than questionable body-surface area. However, all three drugs in the AVI regimen should be monitored simultaneously.

The limits of chemotherapy dose intensification using granulocyte colony stimulating factor alone in extensive small cell lung cancer.

Human Recombinant Granulocyte Colony Stimulating Factor (G-CSF) allows rapid neutrophil recovery after chemotherapy-induced leukopenia. In a prospective series of 54 patients with extensive small cell lung cancer, we evaluated the feasibility and efficacy of accelerated delivery of the AVI chemotherapy regimen. Treatment consisted of Doxorubicin 50 mg/m2 day 1, Etoposide 120 mg/m2 day 1-3 and Ifosfamide 2 g/m2 (+ Mesna 4 g) day 1 and 2 given every 2 weeks and followed by G-CSF (Neupogen, Amgen Roche 5 micrograms/kg/day s.c. day 4-14). Twenty-seven (50%) patients could not receive the total of six courses, seven because of severe septic complication, 10 because of Grade 4 thrombopenia, seven because of non-response and three because of patient refusal. Chemotherapy had to be delayed in 58 out of the 244 administered courses and this was due to thrombopenia in 48% of cases. The probability of optimal dose-on-time administration was 64% at three courses. The mean actually received dose intensity was 93% at six courses (27 patients treated). It was increased by 76% compared to our previously published conventional 3-week interval chemotherapy. The median neutrophil nadirs were stable during the successive treatment courses while haemoglobin and platelet values significantly worsened from cycle 1 to cycle 6. The overall response rate after three courses was 77% in the 48 evaluable patients. The median survival is 8 months overall and 5 months disease free. The actuarial survival is 22% at 2 years. We conclude that substantial dose intensification with accelerated chemotherapy and G-CSF support is feasible. However, the rate of severe infectious episodes is too high and thrombopenia is the main limiting factor. Either growth factors active on the megacaryocytic lineage or haematological rescue with peripheral blood stem cells might be useful in this setting.

A phase II trial of fotemustine and cisplatin in central nervous system metastases from non-small cell lung cancer.

A phase II study was conducted in order to determine the feasibility and toxicity of cisplatin combined with the nitrosourea fotemustine in central nervous system metastases from non-small cell lung cancer. 31 chemotherapy-naïve patients were included between November 1990 and April 1993. Computed tomography scan-documented tumour regression in brain metastases was observed in 7 of the 25 evaluable patients, but only 4 of these (16%) lasted more than 4 weeks. In 2 of these 4 patients, the response on central nervous system metastases was considered as complete. The median duration of response was 20.5 weeks and the median survival was 16 weeks overall and 28.5 weeks for responding patients. The limiting toxicity of this regimen was haematological. 2 patients died from infectious pneumonitis while in neutropenia. Treatment delays due to haematological toxicity occurred in 57% of patients. Despite the rather encouraging response rate, such toxicity appears too high when compared to the overall bad prognosis of this population of patients. Cranial radiotherapy remains the standard treatment in this setting and should only be compared in the future to less aggressive schedules.

[Value of C-reactive protein determination in small cell lung cancer]. / Intérêt du dosage de la protéine C-réactive dans le cancer bronchique à petites cellules.

A prospective analysis of serum levels of C-reactive protein (CRP) has been conducted on a series of 39 small cell lung cancer (SCLC) patients during the first course of chemotherapy in order to evaluate the predictive value of this marker on tumoral extension at diagnosis and response to therapy. Serum levels of CRP were measured before chemotherapy (day 0) and during the first two days of treatment (day 1, day 2). Twenty-three of 32 evaluable patients (71%) had extensive disease. The mean pre-treatment CRP level was significantly higher in this group than in the group of patients with limited disease (52.3 mg/l vs 15.8 mg/l, P = 0.02). Twenty-three patients responded to treatment and nine did not. The evolution of serum CRP levels in both groups was compared between day 0 and day 2. A more than two-fold increase of initial CRP levels showed a 100% predictive value for response. On the other hand, a decrease by more than 50% of initial serum levels was associated with a negative predictive value of 75% for response. We conclude that the follow-up of CRP levels during initial chemotherapy of SCLC might be useful in the initial evaluation of tumoral extension and in the early prediction of response to therapy.

[Comparison of 2 cisplatin and etoposide dosages in relapsing small cell lung cancer]. / Comparison de deux dosages de cisplatine et étoposide dans le cancer bronchique à petites cellules en rechute. (Groupe lyonnais d'oncologie thoracique).

The synergistic combination of cisplatinum and etoposide appears as the best second line treatment in patients relapsing from small cell lung carcinoma (SCLC). In order to test the dose-effect relationship of cisplatinum and etoposide in this situation, we have performed a randomised phase II trial comparing 2 five-day regimens: cisplatinum 20 mg/m2/day+etoposide 60 mg/m2/day (arm A) versus cisplatinum 40 mg/m2/day+etoposide 100 mg/m2/day (arm B) every 4 weeks. Thirty-seven patients were included (arm A: 18, arm B: 19), and 32 were considered to be eligible (arm A: 15, arm B: 17). Eight patients were non evaluable, five of them because of toxic death occurring prior to the second course (arm A: one from neutropenia; arm B: three from neutropenia and one from thrombopenia). The two groups were well balanced with regard to the main prognostic factors (age, sex, performance status, LDH level, response to induction chemotherapy). An objective response was observed in 10/24 evaluable patients (arm A: 4, arm B: 6) and was considered as complete in one patient in arm A and in 2 pts in arm B; these two patients presented with cerebral metastases and their response lasted 9 and 15 weeks respectively. The mean duration of response was 11 weeks in arm A and 10.5 weeks in arm B. The median actuarial survival of the overall population of eligible patients was 15 weeks: 13 weeks in arm A and 16.5 weeks in arm B. The study was discontinued because of the 23.5% toxic deaths rate in the high doses arm in this heavily pre-treated population of patients. However, the high response rate (54% overall, 35% considering toxic death as a failure) is impressive and presents evidence for the dose/effect relationship in SCLC.

[Resection of bronchial carcinoid tumor with the YAG-Nd laser under local anesthesia]. / Résection d'une tumeur carcinoïde bronchique au laser YAG-Nd sous anesthésie locale.

The YAG-Nd laser has been used for several years in tracheobronchial pathology. The authors report the case of an inoperable female patient with a carcinoid tumour of the left main bronchus. The laser resulted in complete removal of obstruction with an excellent clinical, radiological and isotope scan result.

[Chronic idiopathic eosinophilic pneumopathies. A study of 16 cases]. / Pneumopathies chroniques idiopathiques à éosinophiles. Etude de 16 cas.

We report 16 cases of chronic idiopathic interstitial pneumonia (P.C.I.E.). P.C.I.E. has well defined clinical, radiological and biological characteristics which enable the eosinophilic pulmonary infiltrates to be recognised and the diagnosis to be confirmed without histological proof. The data from broncho-alveolar lavage (L.B.A.) show that besides the radiological infiltrates, there is a diffuse alveolar eosinophilia; sometimes confirming the pulmonary function results, which show a similar pattern to diffuse interstitial pneumonia (P.I.D.). The frequent association of asthma (50%) and extra-pulmonary signs (30%) may suggest a vasculitis or more particularly the Churg-Strauss syndrome, all the more so without a lung biopsy; however the evolution of the disease and the response to low dose steroid therapy is against the latter two being considered in the differential diagnosis. The prognosis for P.C.I.E. is good in the short and medium term; nevertheless during the period under observation (mean 6.3 years) steroid therapy could only be stopped in 3 out of 16 patients. The other patients were stable with a low dose of Cortisone. No patient with P.C.I.E. associated with asthma or hypergammaglobulinaemia or extra-pulmonary signs could be weaned from steroids. The authors advocate that the dose of steroids should be adjusted as low as possible to maintain an eosinophilia below 500/mm3.

[Extensive venous thrombosis disclosing an aneurysm of the common iliac artery]. / Thrombose veineuse extensive révélatrice d'un anévrysme de l'artère iliaque primitive.

Although aneurysms of the common iliac artery are a rare occurrence they should be investigated routinely in patients with urinary or thrombo-embolic venous manifestations in the pelvis minor. Clinical signs are inconstant and diagnosis requires the use of abdominopelvic ultrasound tomography. Venous and urinary complications constitute warning signals suggesting the need for surgery to avoid sudden or untimely rupture. Operation in patients with a poor general condition should be performed as a function of the course of the lesion.

[Drug induced pulmonary disease. Diffuse interstitial pneumonitis during chemoradiotherapy for small cell carcinoma of the lung. Two cases (author's transl)]. / A propos des pneumopathies médicamenteuses. Deux observations de pneumopathie interstitielle diffuse au cours du traitement des cancers bronchiques à petites cellules. Rôle probable du cyclophosphamide.

Two patients with small cell carcinoma of the lung treated by chemoradiotherapy developed, diffuse interstitial pneumonitis after 7 and 21 months of treatment while in complete remission of their malignant disease. One patient died after an acute respiratory distress syndrome, but the second improved after steroid therapy and discontinuation of cytotoxic therapy. Pulmonary toxicity appeared to be related to cyclophosphamide therapy, but radiation therapy could have potentiated cyclophosphamide toxicity as it has been shown in bleomycin lung disease.

[Pleural effusion in rheumatoid arthritis (R.A.). Biochemical study of the pleural fluid (author's transl)]. / Les pleurésies rhumatoïdes: intérêt de l'étude biologique du liquide pleural.

The diagnosis of pleural effusion in R.A. is largely done by exclusion. Histopathological data, obtained by pleural punch-biopsy, are unreliable. It is generally a serofibrinous pleural effusion. Biochemical study of the pleural fluid shows a high protein level (> 40 g/l), high latex factor (larger than or equal to 1/2560) and, predominantly, low sugar rate in pleural fluid (< 0,35 g/l) and low complement level (whole hemolytic complement C3 and C4).